Whole genome sequencing reveals a frameshift mutation and a large deletion in YY1AP1 in a girl with a panvascular artery disease.

BACKGROUND: Rare diseases are pathologies that affect less than 1 in 2000 people. They are difficult to diagnose due to their low frequency and their often highly heterogeneous symptoms. Rare diseases have in general a high impact on the quality of life and life expectancy of patients, which are in general children or young people. The advent of high-throughput sequencing techniques has improved diagnosis in several different areas, from pediatrics, achieving a diagnostic rate of 41% with whole genome sequencing (WGS) and 36% with whole exome sequencing, to neurology, achieving a diagnostic rate between 47 and 48.5% with WGS. This evidence has encouraged our group to pursue a molecular diagnosis using WGS for this and several other patients with rare diseases. RESULTS: We used whole genome sequencing to achieve a molecular diagnosis of a 7-year-old girl with a severe panvascular artery disease that remained for several years undiagnosed. We found a frameshift variant in one copy and a large deletion involving two exons in the other copy of a gene called YY1AP1. This gene is related to Grange syndrome, a recessive rare disease, whose symptoms include stenosis or occlusion of multiple arteries, congenital heart defects, brachydactyly, syndactyly, bone fragility, and learning disabilities. Bioinformatic analyses propose these mutations as the most likely cause of the disease, according to its frequency, in silico predictors, conservation analyses, and effect on the protein product. Additionally, we confirmed one mutation in each parent, supporting a compound heterozygous status in the child. CONCLUSIONS: In general, we think that this finding can contribute to the use of whole genome sequencing as a diagnosis tool of rare diseases, and in particular, it can enhance the set of known mutations associated with different diseases.

Caracterización del acoso escolar en niños de 9 a 11 años asistidos en un prestador público y uno privado en Montevideo / Description of bullying among children of 9 to 11 years of age assisted at a public and at a private health provider in Montevideo / Descrição do bullying entre crianças de 9 a 11 anos de idade assistidas num provedor de saúde público e no outro provedor privado em Montevidéu

Resumen: Introducción: el acoso escolar es el maltrato continuo y deliberado hacia un niño o adolescente por parte de otro u otros. Es un problema universal, difícil de identificar en la práctica pediátrica. Objetivo: describir el índice global de acoso y sus características en niños y adolescentes de 9 a 11 años hospitalizados o asistidos en policlínicas en Montevideo. Material y método: estudio transversal. Se incluyeron usuarios de 9 a 11 años, procedentes de Montevideo, hospitalizados o asistidos en policlínica de un prestador público y otro privado durante julio a setiembre de 2017. Variables: sexo, edad, prestador de salud, rendimiento escolar, centro educativo, uso de psicofármacos, índice de masa corporal. Mediante autotest Cisneros se determinó el índice global de acoso e intensidad de este. Fue aprobado por los comités de ética de ambas instituciones. Resultados: se incluyeron 83 niños: 52% niñas; 34% 9 años, 38% 10 años, 28% 11 años; prestador de salud privado 54%; educación pública 88%; buen rendimiento escolar 59%; sobrepeso 18%, obesidad 16%; uso de psicofármacos 16%. El índice global de acoso fue bajo 51%, alto 38%. Se encontró asociación entre alto riesgo de bullying con tipo de centro educativo, uso de psicofármacos e ingreso por motivo psicosocial. Intensidad de acoso alta en 73%. Modalidades más frecuentes: exclusión social y hostigamiento verbal. Conclusiones: se encontró alto riesgo de bullying y su intensidad y modalidad constituyen un problema preocupante.

Summary: Introduction: Bullying is a continuous and deliberate abuse of a child or adolescent by another. It is a global problem, and it usually goes undetected during the pediatric practice. Objective: to develop and describe a global bullying index in children and adolescents aged 9-11 years hospitalized or assisted at a public and at a private health institution in Montevideo. Materials and methods: cross-sectional study. Children from 9 to 11 years of age, from Montevideo, hospitalized or assisted at a public and at a private health institution during July to September 2017. Variables: sex, age, health provider, school performance, school center, use of psychotropic drugs, body mass index. The Cisneros Autotest described the Global Bullying Index and the Bullying Intensity. The methods were approved by the Ethics Committees of both participating health institutions. Results: 83 children participated in the study: 52% girls; 34% 9 years old, 38% 10 years old, 28% 11 years old; 54% from private health provider, 88% from public education system. 59% had good school performance; overweight 18%, obesity 16%; use of psychoactive drugs 16%. The global bullying rate was low 51%, high 38%. We found a link between high risk of bullying and type of school, use of psychotropic drugs and psychosocial admission diagnosis. Intensity was high in 73%. The most common type of bullying described was "social exclusion" and "verbal harassment". Conclusions: we found high-risk of bullying, and found that its intensity and modality have become increasingly concerning.

Resumo: Introdução: o bullying é o abuso contínuo e deliberado de uma criança ou adolescente por parte de uma outra. É um problema global, difícil de identificar na prática pediátrica. Objetivo: descrever o índice global de bullying e suas características em crianças e adolescentes de 9 a 11 anos de idade hospitalizados ou assistidos em policlínicas em Montevidéu. Materiais e métodos: estudo transversal. Foram incluídos usuários entre 9 e 11 anos de idade, procedentes de Montevidéu, hospitalizados ou assistidos numa policlínica de prestador público de saúde e numa privada, entre julho e setembro de 2017. Variáveis: sexo, idade, profissional de saúde, desempenho escolar, escola, uso drogas psicoativas, índice de massa corporal. O índice global de assédio e a sua intensidade foram avaliados através do "Autotest Cisneros". Os resultados foram aprovados pelos comitês de ética de ambas as instituições de saúde. Resultados: incluíram-se 83 meninos: 52% meninas; 34% 9 anos, 38% 10 anos, 28% 11 anos; prestador de serviços de saúde privado 54%; educação pública 88%; bom desempenho escolar 59%; sobrepeso 18%, obesidade 16%; 16% usam drogas psicoativas. A taxa de assédio global foi baixa de 51%, alta de 38%. Foi encontrada associação entre alto risco de bullying com o tipo de escola, uso de drogas psicotrópicas e admissão por razões psicossociais. Intensidade de assédio alta em 73%. Modalidades mais frequentes: "Exclusão social" e "Assédio verbal" Conclusões: encontrou-se um alto risco de bullying cuja intensidade e modalidade são um problema preocupante.